The prevailing paradigm of organizing the supply of blood units available for transfusion relies on routine typing of transfusion antigens by hemagglutination. Typically, the major transfusion antigen groups, namely A, B, O and D, are typed at collection while a select set of minor group antigens such as RhCE, Kell and Kidd are typed only as needed For blood group antigens other than ABO and D, source material is diminishing, and the cost of FDA-approved commercial reagents is escalating. Many antibodies used for testing for minor blood group antigens (especially when searching for an absence of a high prevalence antigen) are not FDA-approved and are characterized to varying degrees by those who use them. In addition, some antibodies are limited in volume, weakly reactive, or not available. Collectively, the labor-intensive approach limits the number of donors one can test; thereby restricting the supply of antigen-negative RBC products for patients who have produced the corresponding alloantibody, and, more recently, restricting the supply of Rh and K matched RBCs for patients in the Stroke Prevention Trial (STOP) program, which was designed to prevent immunization of such patients.
Recipients exposed to foreign transfusion antigens generally will form antibodies directed against those antigens. Allo-immunized patients, a subpopulation comprising approximately 2% of transfused patients, and up to 38% of multiply transfused patients, require red blood cell products which do not contain the offending antigen. Such units typically must be found either in the limited available supply or must be found, in real time, by serological typing of such likely candidate units as may be available in inventory. The selection of candidate units for “stat” typing, performed in immunohematology laboratories, is guided largely by empirical factors. The delay introduced by the search for matching units can exacerbate emergency situations and generally will incur substantial cost to hospitals and/or insurance carriers by delaying in-hospital stay. More generally, allo-immunization to red blood cell antigens which are also displayed on other cells (see Table I) and recognized by certain pathogens such as malaria, can introduce unnecessary health risks whose elimination would improve the general health.
The procurement of matched blood to recipients who either display an uncommon antigen or lack a common antigen, is particularly problematic. While such incidences are considered “rare,” occurring at a rate of one in 1,000 recipients, the supply of matched units is very limited. Thus, existing national collections of special units, including the American Rare Donor Program (ARDP), register donors encountered in the immunohematology laboratories of its members: only 30,000 donors have been registered (see, e.g., the Red Cross Website). In comparison, the National Marrow Donor Program (NMDP), a national registry of prospective bone marrow donors who have been genotyped for polymorphisms in certain loci of the Human Leukocyte Antigen (HLA) gene complex, in the year 2000, comprised 2.7 million fully characterized and 4.1 million known donors to supply matching bone marrow transplants for only ˜2,400 transplantations per year. See, e.g., the National Marrow Donor Program Website
Distribution of the precious few special units available in the program also leaves substantial room for improvement. At present, relying primarily on telephone contacts, only 1,000 special units are placed per year, while up to 2% of the approximately 4-5 million recipients of blood transfusions per year, that is 100,000 recipients, would benefit from improved availability.
In view of this situation, a method of providing a large and diverse inventory of fully typed blood units, and a method of instant and efficient distribution of units in response to requests posted to a central registry would be desirable in order to improve the public health and to minimize the cost accruing in the health care system in the form of unnecessarily prolonged hospital stays, adverse transfusion reactions (see Hillyer et al., Blood Banking and Transfusion Medicine; published by Churchill Livingston, Philadelphia Pa.) and other potential complications arising from allo-immunization.
However, absent substantial government or private funding for such an endeavor, a registry of “critical mass” must be created and operated in a commercially viable manner. The ARDP operation, representative of current practice, illustrates the difficulty: In order to identify a special donor, up to 1,000 donors may have been typed, and from a collection of 30,000 such special units, only 1,000 were placed. While special units fetch a higher price than do “vanilla” red blood cell products, the premium does not come close to covering the cost, in view of the substantial amount of excess typing required. Commercial viability, under these conditions, is doubtful.